lincRNA-EPS在LPS诱导性牙周炎发生发展中的作用及其机制研究

LincRNA plays a role in the inflammatory response, but also is a key factor in the regulation of immune function.LincRNA-EPS has recently been found to precisely regulate the expression of macrophage of immune response genes (IRGs) .In the early stage of this project,the expression of lincRNA-EPS in periodontal tissues of mice stimulated by LPS was significantly decreased. Meanwhile, we successfully knocked out lincRNA-EPS in mice, and found that the inflammation of periodontal tissue was worse than before, but its mechanism was not clear yet. Based on previous studies, we prepare to establish lincRNA-EPS knockout model by LPS-induced periodontitis in mice to study the role of lincRNA-EPS in the occurrence and development of periodontitis, to find the protein which can combine with lincRNA-EPS, to analyze the role of lincRNA-EPS / NLRP3 / inflammation-related caspases so as to reveal its regulatory mechanism. At the same time, we will fabricate lincRNA-EPS delivery system, introduce exogenous lincRNA-EPS to ‘cure’ periodontitis in the model mice for studying the role of exogenous lincRNA-EPS of immunoregulatory effect in periodontal tissues and exploring the targeted remedies, thereby providing a new theoretical foundation for the treatment of periodontitis.

lincRNA不仅在炎症反应中发挥作用，而且是调控免疫功能的关键因子，lincRNA-EPS被发现能精确调控巨噬细胞免疫应答基因的表达，本项目组前期发现LPS诱导性牙周炎小鼠的牙周组织中lincRNA-EPS表达明显降低；敲除小鼠lincRNA-EPS后，小鼠牙周炎明显加重，但其机制尚不清楚。本项目在前期研究的基础上，拟构建lincRNA-EPS敲除的LPS诱导性牙周炎小鼠模型，研究lincRNA-EPS在牙周炎发生发展中的作用，找出与lincRNA-EPS相结合的关键蛋白，分析lincRNA-EPS/NLRP3/炎症相关caspases发挥的作用，并揭示其调控机制。同时构建lincRNA-EPS递送系统，引入外源性lincRNA-EPS，“挽救”疾病模型小鼠牙周炎，研究外源性lincRNA-EPS在牙周组织中免疫调控的作用，探寻有针对性的牙周炎治疗方法，从而为牙周炎治疗提供新的理论依据。

牙周炎是口腔常见的一种慢性感染性疾病，可严重危害口腔以及全身身心健康。牙周炎的主要致病菌是革兰氏阴性厌氧杆菌，它的毒力因子---细菌外膜成分脂多糖（LPS），能直接作用于牙周组织细胞，引起牙周组织的破坏。研究表明，lincRNA不仅在炎症反应中发挥作用，而且是调控免疫功能的关键因子。lincRNA-EPS被发现能精确调控巨噬细胞免疫应答基因的表达。本项目组早期实验发现LPS诱导性牙周炎小鼠其牙周组织内lincRNA-EPS表达显著降低，lincRNA-EPS敲除后，小鼠牙周炎明显加重，但其机制尚不清楚。.在前期研究基础上，本项目组成功构建lincRNA-EPS敲除的LPS诱导性牙周炎小鼠模型，明确lincRNA-EPS缺陷小鼠在LPS刺激下加重牙周组织炎症反应的具体表型特征；采用高通量测序等技术检测lincRNA-EPS基因敲除前后、LPS诱导下牙周组织细胞全基因组基因表达变化，通过PPI、KEGG分析及GO注释，寻找差异炎症基因和信号通路，并探索潜在的lincRNA-EPS互作蛋白；同时分析了lincRNA-EPS/NLRP3/炎症相关caspases发挥作用的机制。随后设计并合成lincRNA-EPS递送系统，建立易于纳米粒包裹的lincRNA-EPS过表达重组质粒，引入外源性lincRNA-EPS，“挽救”了疾病模型小鼠牙周组织炎症，进一步分析lincRNA-EPS在牙周组织中的调控作用，并探讨其对牙周炎有针对性疗效的治疗方法。.研究结果对于解除牙周炎患者的痛苦，提高牙周炎治疗疗效等方面有着重要的理论意义和巨大的临床应用价值。已在国内外学术刊物上正式发表论文12篇，其中SCI收录论文5篇。在全国学术会议上发表研究论文6篇。培养研究生4人、博士后1人。